Format

Send to

Choose Destination
See comment in PubMed Commons below
Brain Dev. 2014 Apr;36(4):351-5. doi: 10.1016/j.braindev.2013.05.001. Epub 2013 May 28.

The first case of CDK5RAP2-related primary microcephaly in a non-consanguineous patient identified by next generation sequencing.

Author information

  • 1Department of Human Genetics, University of Chicago, 5841 S. Maryland Ave, MC 0077, Chicago, IL 60637, USA. Electronic address: ctan@bsd.uchicago.edu.
  • 2Department of Human Genetics, University of Chicago, 5841 S. Maryland Ave, MC 0077, Chicago, IL 60637, USA.
  • 3Division of Medical Genetics, Akron Children's Hospital, One Perkins Square, Akron, OH 44308, USA.

Abstract

Primary autosomal recessive microcephaly (MCPH) is a genetically heterogeneous condition characterized by congenital microcephaly and intellectual disability. To date, 10 MCPH loci have been identified and due to the genetic heterogeneity of this condition, molecular testing for MCPH can be complicated. Our methods involved employing a next generation sequencing panel of MCPH-related genes allowing for the evaluation of multiple disease loci simultaneously. Next generation sequencing analysis of a 6 year old female with primary microcephaly identified novel compound heterozygous mutations (c.524_528del and c.4005-1G>A) in the CDK5RAP2 gene. A review of the published literature to date reveals that only three mutations have been previously reported in the CDK5RAP2 gene in the homozygous state in three Northern Pakistani and one Somali consanguineous MCPH families. Our patient represents the first non-consanguineous Caucasian individual to have been identified with CDK5RAP2-related MCPH. As only a handful of patients have been reported in the literature with CDK5RAP2-related MCPH, we anticipate the identification of individuals with CDK5RAP2 mutations from all ethnic backgrounds will continue. Our patient contributes to the ethnic and genotypic spectrum of CDK5RAP2-related MCPH and supports the occurrence of this genetic condition beyond that of consanguineous families of certain ethnic populations. Our results also highlight the utility of multi-gene sequencing panels to elucidate the etiology of genetically heterogeneous conditions.

Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

KEYWORDS:

CDK5RAP2; Next generation sequencing; Non-consanguineous; Primary autosomal recessive microcephaly

[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk